Missing content? – Request curation!
Request curation for specific Genes, variants, or PubMed publications.
Have questions, comments or suggestions? - Let us know!
Email us at : firstname.lastname@example.org
|Ref Type||Journal Article|
|Authors||Azad N, Perroy A, Gardner E, Imamura CK, Graves C, Sarosy GA, Minasian L, Kotz H, Raggio M, Figg WD, Kohn EC|
|Title||A phase I study of paclitaxel and continuous daily CAI in patients with refractory solid tumors.|
|Journal||Cancer biology & therapy|
|Abstract Text||Carboxyamido-triazole (CAI) is a calcium influx inhibitor with anti-angiogenic and anti-invasive properties and stabilizes tumor progression in patients. We hypothesized daily oral micronized CAI with q3 week paclitaxel would be well-tolerated and active.Twenty-nine heavily pretreated patients [median 3 [0-7]] were enrolled on five dose levels. No additive or cumulative toxicity was observed, and grade III nonhematological toxicity was rare. Neutropenia was the most common hematologic toxicity, seen in 79% of patients, with a trend towards increasing grade with higher paclitaxel doses. The recommended phase II dose defined by the maximum tolerated dose (MTD) was CAI 250 mg daily and paclitaxel 200 mg/m(2) q3weeks. Pharmacokinetic analysis revealed paclitaxel increases CAI trough concentration at all dose levels by over 100% (p < 0.0001). A trend towards higher steady-state CAI trough concentrations was found in patients with a partial response (PR; p = 0.09). Six patients had confirmed PR (24%; 4-67 cycles, median 10); two patients had minor responses.Eligible patients with solid tumors received micronized CAI daily (150-250 mg PO) and paclitaxel intravenously q3weeks (175-250 mg/m(2)), sequentially escalating each drug. CAI preceded paclitaxel by one week to permit pharmacokinetic analysis. Patients were assessed for toxicity, pharmacokinetics and disease outcome.The MTD of the combination of CAI and paclitaxel is 250 mg daily and 200 mg/m(2) q3weeks, respectively. The combination is tolerable and has potential antitumor activity.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||Carboxyamidotriazole Orotate + Paclitaxel||Phase I||Actionable||In Phase I trial, carboxyamidotriazole in combination with Taxol (paclitaxel) displayed safety and efficacy in patients with solid tumors (PMID: 19738417).||19738417|